Annotation and functional clustering of circRNA expression in rhesus macaque brain during aging

Abstract

The abundance and function of circular RNAs (circRNAs) in mammalian brain have been reported, but their alterations in the biology of brain aging remain elusive. Here, using deep RNA profiling with linear RNA digestion by RNase R we explored a comprehensive map of changes in circRNA expression in rhesus macaque (macaca mulatta) brain in two age groups from adult (10 y) to aged (20 y) periods. Total 17,050 well expressed, stable circRNAs were identified. Cluster analysis reveals that dynamic changes in circRNA expression show the spatial-, sex- and age-biased specificities. On the basis of separate profiling of the RNAs, age-related circRNAs show differential correlation to host mRNA expression. Furthermore, two voltage-dependent L- and R-type calcium channel gene-derived circCACNA2D1 and circCACNA1E negatively regulate their host mRNA expression. Our results demonstrate the power of changes in circRNA expression to reveal insights into a potentially circRNA-mediated regulatory mechanism underlying the biology of brain aging.

Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

“…They are the result of heterogeneous nuclear RNA (hnRNA)/pre-mRNA back-splicing and, as such, represent covalently closed circles, which are devoid of RNA cap structures or terminal poly(A) tails [ 45 , 47 , 48 ]; these features render them substantially different from their corresponding linear mRNA counterparts [ 45 ]. Previous analysis revealed that circRNA formation is most prominent in the brain [ 49 , 50 , 51 ]. Interestingly, in several organisms, circRNAs are regulated in an age-dependent manner [ 51 , 52 , 53 , 54 , 55 , 56 ].…”

An integrated analysis of the circRNA–miRNA–mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration

“…Therefore, Si-circ_19698-1 was selected and used in later experiments due to its higher interference efficacy. Previous research has revealed positive correlations between the circRNA abundance and expression levels of linear host genes in several cell lines or tissues [42,43]. One of our previous studies found that the expression profiles of circ_19698 and Tnfrsf21 (linear host transcript for circ_19698) exhibited similarities during rat LR when detected by qRT-PCR, which demonstrated positive correlations between circ_19698 and Tnfrsf21 [16].…”

Circular RNA LARP4 correlates with decreased Enneking stage, better histological response, and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging microRNA‐424 in osteosarcoma

“…The relative expressions of circ‐LARP4 in the tumor tissue/non‐tumor tissue and miR‐424 in osteosarcoma cells were detected by the qPCR. Firstly, the total RNA was extracted by RNeasy Protect Mini Kit (Qiagen), and then, the RNase R (Epicenter) was used for the digestion of linear RNA for the detection of circ‐LARP4 expression . Secondly, the RNA was reversely transcribed by using the iScript ™ cDNA Synthesis Kit (with random primer) (Bio‐Rad), and qPCR was performed by QuantiNova SYBR Green PCR Kit (Qiagen).…”

“…Firstly, the total RNA was extracted by RNeasy Protect Mini Kit (Qiagen), and then, the RNase R (Epicenter) was used for the digestion of linear RNA for the detection of circ-LARP4 expression. 19 Secondly, the RNA was reversely transcribed by using the iScript ™ cDNA Synthesis Kit (with random primer) (Bio-Rad), and qPCR was performed by QuantiNova SYBR Green PCR Kit (Qiagen). And the reaction condition was as follows: initial denaturation at 95℃ for 5 minutes, and then 40 cycles of denaturation (94℃, 15 seconds), annealing (61℃, 30 seconds), and extending (72 ℃, 30 seconds), and then an extending at 72℃ for 1 minute.…”